Selectivity in tip-induced skeletal editing via heteroatom substitution

Abstract

Skeletal editing enables precise structural modifications of molecules at late stages of a synthetic sequence, with applications in drug discovery and materials science. We recently demonstrated skeletal editing on the single-molecule scale. Voltage pulses applied by the tip of a scanning probe microscope to an oxygen-containing seven-membered heterocycle led to both oxygen deletion and ring-contraction rearrangement reactions. An open question is whether selective skeletal editing of a heterocyclic core can be achieved by an appropriate choice of the heteroatom. Here, we show that tip-induced reactions of an analogous sulfur-containing seven-membered ring results in sulfur deletion in virtually all cases. Our results demonstrate that the combination of tip-induced chemistry and heteroatom selection in the molecular design is a powerful strategy for single-molecule skeletal editing, with the potential to enable diverse structural transformations of heterocyclic frameworks.